The establishment of an AIDS Clinical Trials Unit Core Pharmacology laboratory at the University of Colorado Health Sciences Center (UCHSC) is proposed. This laboratory will serve to support ACTG protocol-mandated requirements for the determination of body fluid levels of therapeutic agents, their metabolites or endogenous substances of interest (e.g., specific cytokines). The therapeutic agents may include antiretroviral drugs as well as agents used in the therapy of opportunistic infections. the laboratory will be expected to adapt, develop and modify assays as needed to serve the needs of specific research protocols and projects. The laboratory will also support, in part, the UCHSC Developmental Pharmacology Group in their proposed studies of drugs metabolized by the hepatic cytochrome P450 system. The previous experience of the applicants is outlined. This includes expertise in diverse methods of biochemical analysis, enzymology, drug screening and development, cell membrane transport, cell culture systems (mammalian and protozoan) and the design and operation of pharmacokinetic trials. Other pertinent experience includes previous ACTU affiliations, and experience in the areas of laboratory quality assurance, infection control and biohazard committees. The applicants outline approaches to developing and implementing an assay for very diverse compounds (zidovudine, foscarnet, and SC-48334) from now- closed ACTG protocols (019,093,100) as suggested in the RFA. The applicants also describe approaches to future assays likely to be requested, including a general approach as well as specific approaches for ddI, ddC, d4T and phosphorylated nucleoside analogue metabolites.